Limits...
Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

Roth A, Glaesener S, Schütz K, Meyer-Bahlburg A - PLoS ONE (2016)

Bottom Line: We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations.Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23.Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

Show MeSH

Related in: MedlinePlus

Kinetics of PnPS-specific IgA, IgM and IgG antibody secreting cells and antibodies.(A) Upper panel: PnPS-specific IgM, IgA and IgG as determined by ELISpot assay (n = 21). Lower panel: Representative ELISpot wells of one donor shown for IgA-producing PBMC on day 0, 7, and 14 after vaccination with Pneumovax®23. (B) PnPS-specific IgM, IgA and IgG ASC in sort-purified CD19+CD27++ plasma blasts/plasma cells, CD19+CD27+ memory B cells and CD19+CD27- naïve B cells at day 7 post-vaccination. (C) Dynamics of PnPS-specific antibody responses in serum from day 0 to day 90 determined by ELISA (n = 30). (D) Positive correlation between PnPS-specific serum IgA on day 7 and IgA-producing cells. (E) Sputum/serum ratio of PnPs-specific Ig on day 28. (F) Positive correlation between PnPS-specific serum IgA on day 14 and IgA in sputum on day 28. Mean values ± SEM are indicated for each time point; (*p<0.05, **p<0.01, ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4816312&req=5

pone.0152215.g004: Kinetics of PnPS-specific IgA, IgM and IgG antibody secreting cells and antibodies.(A) Upper panel: PnPS-specific IgM, IgA and IgG as determined by ELISpot assay (n = 21). Lower panel: Representative ELISpot wells of one donor shown for IgA-producing PBMC on day 0, 7, and 14 after vaccination with Pneumovax®23. (B) PnPS-specific IgM, IgA and IgG ASC in sort-purified CD19+CD27++ plasma blasts/plasma cells, CD19+CD27+ memory B cells and CD19+CD27- naïve B cells at day 7 post-vaccination. (C) Dynamics of PnPS-specific antibody responses in serum from day 0 to day 90 determined by ELISA (n = 30). (D) Positive correlation between PnPS-specific serum IgA on day 7 and IgA-producing cells. (E) Sputum/serum ratio of PnPs-specific Ig on day 28. (F) Positive correlation between PnPS-specific serum IgA on day 14 and IgA in sputum on day 28. Mean values ± SEM are indicated for each time point; (*p<0.05, **p<0.01, ***p<0.001).

Mentions: We next tested the vaccine-induced antigen-specific B cell response in terms of frequency of PnPS-specific ASC, and antibody levels in serum and sputum. PnPS-specific IgA, IgM and IgG producing cells were determined by ELISpot assays. In agreement with previous studies [32], antigen-specific ASC were only detected on day 7 post vaccination (Fig 4A). We found significantly more PnPS-specific IgA ASC (696±414 cells/ml representing 64±30% of average total ASC) compared to PnPS-specific IgM (279±200 cells/ml) and IgG (109±74 cells/ml) ASC.


Reduced Number of Transitional and Naive B Cells in Addition to Decreased BAFF Levels in Response to the T Cell Independent Immunogen Pneumovax®23.

Roth A, Glaesener S, Schütz K, Meyer-Bahlburg A - PLoS ONE (2016)

Kinetics of PnPS-specific IgA, IgM and IgG antibody secreting cells and antibodies.(A) Upper panel: PnPS-specific IgM, IgA and IgG as determined by ELISpot assay (n = 21). Lower panel: Representative ELISpot wells of one donor shown for IgA-producing PBMC on day 0, 7, and 14 after vaccination with Pneumovax®23. (B) PnPS-specific IgM, IgA and IgG ASC in sort-purified CD19+CD27++ plasma blasts/plasma cells, CD19+CD27+ memory B cells and CD19+CD27- naïve B cells at day 7 post-vaccination. (C) Dynamics of PnPS-specific antibody responses in serum from day 0 to day 90 determined by ELISA (n = 30). (D) Positive correlation between PnPS-specific serum IgA on day 7 and IgA-producing cells. (E) Sputum/serum ratio of PnPs-specific Ig on day 28. (F) Positive correlation between PnPS-specific serum IgA on day 14 and IgA in sputum on day 28. Mean values ± SEM are indicated for each time point; (*p<0.05, **p<0.01, ***p<0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4816312&req=5

pone.0152215.g004: Kinetics of PnPS-specific IgA, IgM and IgG antibody secreting cells and antibodies.(A) Upper panel: PnPS-specific IgM, IgA and IgG as determined by ELISpot assay (n = 21). Lower panel: Representative ELISpot wells of one donor shown for IgA-producing PBMC on day 0, 7, and 14 after vaccination with Pneumovax®23. (B) PnPS-specific IgM, IgA and IgG ASC in sort-purified CD19+CD27++ plasma blasts/plasma cells, CD19+CD27+ memory B cells and CD19+CD27- naïve B cells at day 7 post-vaccination. (C) Dynamics of PnPS-specific antibody responses in serum from day 0 to day 90 determined by ELISA (n = 30). (D) Positive correlation between PnPS-specific serum IgA on day 7 and IgA-producing cells. (E) Sputum/serum ratio of PnPs-specific Ig on day 28. (F) Positive correlation between PnPS-specific serum IgA on day 14 and IgA in sputum on day 28. Mean values ± SEM are indicated for each time point; (*p<0.05, **p<0.01, ***p<0.001).
Mentions: We next tested the vaccine-induced antigen-specific B cell response in terms of frequency of PnPS-specific ASC, and antibody levels in serum and sputum. PnPS-specific IgA, IgM and IgG producing cells were determined by ELISpot assays. In agreement with previous studies [32], antigen-specific ASC were only detected on day 7 post vaccination (Fig 4A). We found significantly more PnPS-specific IgA ASC (696±414 cells/ml representing 64±30% of average total ASC) compared to PnPS-specific IgM (279±200 cells/ml) and IgG (109±74 cells/ml) ASC.

Bottom Line: We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations.Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23.Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment.

View Article: PubMed Central - PubMed

Affiliation: Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.

ABSTRACT
Protective immunity against T cell independent (TI) antigens such as Streptococcus pneumoniae is characterized by antibody production of B cells induced by the combined activation of T cell independent type 1 and type 2 antigens in the absence of direct T cell help. In mice, the main players in TI immune responses have been well defined as marginal zone (MZ) B cells and B-1 cells. However, the existence of human equivalents to these B cell subsets and the nature of the human B cell compartment involved in the immune reaction remain elusive. We therefore analyzed the effect of a TI antigen on the B cell compartment through immunization of healthy individuals with the pneumococcal polysaccharide (PnPS)-based vaccine Pneumovax®23, and subsequent characterization of B cell subpopulations. Our data demonstrates a transient decrease of transitional and naïve B cells, with a concomitant increase of IgA+ but not IgM+ or IgG+ memory B cells and a predominant generation of PnPS-specific IgA+ producing plasma cells. No alterations could be detected in T cells, or proposed human B-1 and MZ B cell equivalents. Consistent with the idea of a TI immune response, antigen-specific memory responses could not be observed. Finally, BAFF, which is supposed to drive class switching to IgA, was unexpectedly found to be decreased in serum in response to Pneumovax®23. Our results demonstrate that a characteristic TI response induced by Pneumovax®23 is associated with distinct phenotypical and functional changes within the B cell compartment. Those modulations occur in the absence of any modulations of T cells and without the development of a specific memory response.

Show MeSH
Related in: MedlinePlus